LRP5 deficiency down-regulates Wnt signalling and promotes aortic lipid infiltration in hypercholesterolaemic mice
Borrell-Pages, Maria (Institut d'Investigació Biomèdica Sant Pau)
Romero, July Carolina (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2015
Abstract:	Low-density lipoprotein receptor-related protein 5 (LRP5) is a member of the LDLR family that orchestrates cholesterol homoeostasis. The role of LRP5 and the canonical Wnt pathway in the vascular wall of dyslipidaemic animals remains unknown. In this study, we analysed the role of LRP5 and the Wnt signalling pathway in mice fed a hypercholesterolaemic diet (HC) to trigger dyslipidaemia. We show that Lrp5 mice had larger aortic lipid infiltrations than wild-type mice, indicating a protective role for LRP5 in the vascular wall. Three members of the LDLR family, Lrp1, Vldlr and Lrp6, showed up-regulated gene expression levels in aortas of Lrp5 mice fed a hypercholesterolaemic diet. HC feeding in Lrp5 mice induced higher macrophage infiltration in the aortas and accumulation of inflammatory cytokines in blood. Wnt/β-CATENIN signalling proteins were down-regulated in HC Lrp5 mice indicating that LRP5 regulates the activation of Wnt signalling in the vascular wall. In conclusion, our findings show that LRP5 and the canonical Wnt pathway down-regulation regulate the dyslipidaemic profile by promoting lipid and macrophage retention in the vessel wall and increasing leucocyte-driven systemic inflammation.
Grants:	Ministerio de Ciencia e Innovación SAF2010-16549 Ministerio de Economía y Competitividad RD12/0019/0026 Ministerio de Economía y Competitividad RD12/0042/0027
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Atherosclerosis ; Canonical Wnt signalling ; LRP5 ; Macrophages ; Plasma cholesterol
Published in:	Journal of Cellular and Molecular Medicine, Vol. 19 Núm. 4 (january 2015) , p. 770-777, ISSN 1582-4934

DOI: 10.1111/jcmm.12396
PMID: 25656427

8 p, 686.7 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles